RET signaling is essential for migration, axonal growth and axon guidance of developing sympathetic neurons

Sympathetic axons use blood vessels as an intermediate path to reach their final target tissues. The initial contact between differentiating sympathet ic neurons and blood vessels occurs following the primary sympathetic chain formation, where precursors of sympathetic neurons migrate and project axo ns along or toward blood vessels. We demonstrate that, in Ret-deficient mic e, neuronal precursors throughout the entire sympathetic nervous system fai l to migrate and project axons properly. These primary deficits lead to mis -routing of sympathetic nerve trunks and accelerated cell death of sympathe tic neurons later in development. Artemin is expressed in blood vessels dur ing periods of early sympathetic differentiation, and can promote and attra ct axonal growth of the sympathetic ganglion in vitro. This analysis identi fies RET and artemin as central regulators of early sympathetic innervation .